
This AOP is licensed under a Creative Commons Attribution 4.0 International License.
Aop: 428
Title
Binding of S-protein to ACE2 in enterocytes induces ACE2 dysregulation leading to gut dysbiosis
Short name
Graphical Representation
Point of Contact
Contributors
- Laure-Alix Clerbaux
- Julija Filipovska
- Cataia Ives
Status
Author status | OECD status | OECD project | SAAOP status |
---|---|---|---|
Under development: Not open for comment. Do not cite | Under Development | 1.96 | Included in OECD Work Plan |
This AOP was last modified on July 16, 2022 18:37
Revision dates for related pages
Page | Revision Date/Time |
---|---|
Binding to ACE2 | May 17, 2022 10:20 |
Dysregulation, ACE2 expression and activity | December 05, 2021 12:24 |
Gut microbiota, alteration | January 04, 2022 10:31 |
Binding to ACE2 leads to ACE2 dysregulation | February 12, 2022 08:14 |
ACE2 dysregulation leads to Gut dysbiosis | December 02, 2021 07:16 |
Abstract
S-protein binding to ACE2 receptor induces dysregulation of ACE2 physiological functions in the intestines such as modulation of the local renin-angiotensin signaling (RAS) system (10.1152/ajpgi.00099.202) or as a chaperone for dietary amino acid (AA) transporters in the intestines, such as the tryptophan transporter B0AT1 (Slc6a19) (10.1042/CS20200477; 10.1053/j.gastro.2008.10.055). The gastrointestinal RAS appears to be involved in numerous processes in the gut including AA, fluid and electrolyte absorption and secretion (10.1111/j.1365-2036.2011.04971.x.). Besides, the gut microbiota is influenced by the host intestinal AA metabolism as gut bacteria use dietary AA for protein synthesis (10.1038/s41598-020-74122-9).
AOP Development Strategy
Context
AOP428 is developed as a part of the CIAO project, "Modelling the Pathogenesis of COVID-19 Using the Adverse Outcome Pathway (AOP)". The overall goal is to organize and understand the vast amount of data that is constantly evolving as a result of the COVID-19 pandemic and identify uncertainties and knowledge gaps that may be missing using the AOP framework. Many AOPs were developed in the CIAO project, each AOP focusing on a specific element of the SARS-COV-2 virus responses in humans.
AOP428 focuses on the intestinal part and alteration of the gut microbiota via ACE2 dysregulation.
Strategy
Summary of the AOP
Events:
Molecular Initiating Events (MIE)
Key Events (KE)
Adverse Outcomes (AO)
Type | Event ID | Title | Short name |
---|
MIE | 1739 | Binding to ACE2 | Binding to ACE2 |
KE | 1854 | Dysregulation, ACE2 expression and activity | ACE2 dysregulation |
KE | 1954 | Gut microbiota, alteration | Gut dysbiosis |
Relationships Between Two Key Events (Including MIEs and AOs)
Title | Adjacency | Evidence | Quantitative Understanding |
---|
Binding to ACE2 leads to ACE2 dysregulation | adjacent | Moderate | |
ACE2 dysregulation leads to Gut dysbiosis | adjacent | Moderate | Moderate |